Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs

Wang, Jianglin; Ren, Changhe; Feng, Jian; Ou, Cehua; Liu, Li

doi:10.1016/j.biopha.2019.109752

Cited by 48 publications

(36 citation statements)

References 53 publications

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“…In the present work, we have detected an increase in the phosphorylation of p38 protein. Activation of this MAPK is involved in cell death [ 55 ]. Moreover, it has been shown that melatonin-induced cell death involves phosphorylation of p38 [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Estarás

Gonzalez

Fernandez–Bermejo

et al. 2021

IJMS

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In certain diseases of the pancreas, pancreatic stellate cells form an important part of fibrosis and are critical for the development of cancer cells. A hypoxic condition develops within the tumor, to which pancreatic stellate cells adapt and are able to proliferate. The consequence is the growth of the tumor. Melatonin, the product of the pineal gland, is gaining attention as an agent with therapeutic potential against pancreatic cancers. Its actions on tumor cells lead, in general, to a reduction in cell viability and proliferation. However, its effects on pancreatic stellate cells subjected to hypoxia are less known. In this study, we evaluated the actions of pharmacological concentrations of melatonin (1 mM–1 µM) on pancreatic stellate cells subjected to hypoxia. The results show that melatonin induced a decrease in cell viability at the highest concentrations tested. Similarly, the incorporation of BrdU into DNA was diminished by melatonin. The expression of cyclins A and D also was decreased in the presence of melatonin. Upon treatment of cells with melatonin, increases in the expression of major markers of ER stress, namely BIP, phospho-eIF2α and ATF-4, were detected. Modulation of apoptosis was noticed as an increase in caspase-3 activation. In addition, changes in the phosphorylated state of p44/42, p38 and JNK MAPKs were detected in cells treated with melatonin. A slight decrease in the content of α-smooth muscle actin was detected in cells treated with melatonin. Finally, treatment of cells with melatonin decreased the expression of matrix metalloproteinases 2, 3, 9 and 13. Our observations suggest that melatonin, at pharmacological concentrations, diminishes the proliferation of pancreatic stellate cells subjected to hypoxia through modulation of cell cycle, apoptosis and the activation of crucial MAPKs. Cellular responses might involve certain ER stress regulator proteins. In view of the results, melatonin could be taken into consideration as a potential therapeutic agent for pancreatic fibrosis.

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Section: Discussionmentioning

confidence: 99%

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Estarás

Gonzalez

Fernandez–Bermejo

et al. 2021

IJMS

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“…We found that after OGD/R induction, cell activity decreased, aggravated inflammatory response and significantly increased apoptosis level, indicating the successful establishment of the model OA is a broad-spectrum antimicrobial drug, which is widely used in the treatment of inflammatory diseases and infectious diseases. 12,13 Research showed that OA can improve dietinduced obesity by modulating fat preference and fever in mice. 14 OA can inhibit inflammatory cell infiltration, reduce oxidative stress response of cells, and inhibit cell apoptosis, thus playing a protective role in lung injury of mice.…”

Section: Discussionmentioning

confidence: 99%

Oleanolic Acid Improved Inflammatory Response and Apoptosis of PC12 Cells Induced by OGD/R Through Downregulating miR-142-5P

Gu¹

2021

Natural Product Communications

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Background Oleanolic acid (OA) has notable anti-inflammatory and anti-tumor effects, but the role of OA in cerebral ischemia-reperfusion injury (CIRI) has not been reported so far. Methods Oxygen and glucose deprivation/reoxygenation (OGD/R) model was induced in PC12 cells. MTT assay was used to detect the cell viability of PC12 cells, while ELISA assay detected the expression of TNF-α, IL-1β and IL-6. The expression of superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) was detected by the appropriate kits, and cell apoptosis by Tunel technique. Western blot assay detected the expression of apoptosis-related proteins. The cell transfection technique overexpressed miR-142‐5p. After overexpressing miR-142‐5p by cell transfection technique, the expression of miR-142‐5p was detected by RT-qPCR. Results Besides the ability to promote cell acitivity, OA ameliorated OGD/R-induced inflammatory response and apoptosis in PC12 cells. Moreover, the capability of OA to alleviate OGD/R-induced inflammation and apoptosis in PC12 cells was observed to be related to the down-regulation of miR-142‐5p. Conclusion OA improved inflammatory response and apoptosis of PC12 cells induced by OGD/R through downregulating miR-142‐5P

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“…Its mechanism was related to inhibition of MAPKs and NF-κB signaling pathways in SCI mice, as evidenced by the down-regulated phosphorylation of p38, c-Jun-NH 2 terminal kinase (JNK), IκB kinase α (IKKα) and NF-κB. 154 Lycopene is a natural carotenoid mostly found in tomato, watermelons and papayas, and proves useful in managing neurodegenerative disorders. 155 BSCB restoration is an effective pathway for lycopene in SCI treatment.…”

Section: Dovepressmentioning

confidence: 99%

Neuroinflammation and Modulation Role of Natural Products After Spinal Cord Injury

Yan

Zhang

2021

JIR

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Oleanolic acid inhibits mouse spinal cord injury through suppressing inflammation and apoptosis via the blockage of p38 and JNK MAPKs

Cited by 48 publications

References 53 publications

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Melatonin Induces Apoptosis and Modulates Cyclin Expression and MAPK Phosphorylation in Pancreatic Stellate Cells Subjected to Hypoxia

Oleanolic Acid Improved Inflammatory Response and Apoptosis of PC12 Cells Induced by OGD/R Through Downregulating miR-142-5P

Neuroinflammation and Modulation Role of Natural Products After Spinal Cord Injury

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